Archaic human admixture with modern Homo sapiens is known to have occurred at least twice in history: with Neanderthals, and with the Denisova hominin. A minimum estimated 1 to 4 percent of the DNA in Europeans and Asians (i.e. French, Chinese and Papua probands) is non-modern, and shared with ancient Neanderthal DNA rather than with Sub-Saharan Africans (i.e. Yoruba and San probands).[1][2] A minimum additional estimated 4-6% of Melanesian DNA is from the archaic Denisovan hominins from Asia.[3] Recent DNA analysis also indicates Sub-Saharan African admixture with a now extinct archaic population. [4]

The hypothesis, variously under the names of interbreeding, hybridization, admixture or hybrid-origin theory, has been discussed ever since the discovery of Neanderthal remains in 19th century, though earlier writers believed that Neanderthals were a direct ancestor of modern humans. Thomas Huxley suggested that many Europeans bore traces of Neanderthal ancestry, but associated Neanderthal characteristics with primitivism, writing that since they "belong to a stage in the development of the human species, antecedent to the differentiation of any of the existing races, we may expect to find them in the lowest of these races, all over the world, and in the early stages of all races."[8]

In the early twentieth century, Carleton Coon argued that the Caucasoid race is of dual origin consisting of Upper Paleolithic (mixture of H. sapiens and neanderthalensis) types and Mediterranean (purely H. sapiens) types. He repeated his theory in his 1962 book The Origin of Races.[9]

Stan Gooch in Personality and Evolution (1973) and The Neanderthal Question (1977) develops a theory of Neanderthal/Cro-Magnon hybridization, based not on an examination of anatomy but of his understanding of modern human psychology and society, which he claimed owes a significant debt to Neanderthal culture. Gooch's theories were dismissed by academia. Gooch refined his theory in Cities of Dreams (1989) and The Neanderthal Legacy (2008).

A draft sequence publication by the Neanderthal Genome Project in May 2010 indicates that Neanderthals share more genetic lineages with Non-African populations than with African populations. According to the study, this scenario is best explained by gene flow from Neanderthals to modern humans after humans emerged from Africa. An estimated 1 to 4 percent of the DNA in Europeans and Asians (e.g. French, Chinese and Papua probands) is non-modern, and shared with ancient Neanderthal DNA rather than with Sub-Saharan Africans (e.g. Yoruba and San probands). Though less parsimonious than gene flow, ancient sub-structure in Africa, could account for the higher levels of Neanderthal lineages detected in Eurasians. [10]

No evidence supporting this has been found in mitochondrial DNA analyses of modern Europeans, suggesting at least that no direct maternal line originating with Neanderthals has survived into modern times.[11][12][13]

Variation in microcephalin, a critical regulator of brain size whose loss-of-function by damaging mutations may also cause primary microcephaly, was claimed to be the strongest evidence of admixture as of 2007. One type of the gene, known as D, has a high worldwide frequency (~70%), but a young coalescence age to its most recent common ancestor, ~37,000 years ago. The remaining types (non-D) coalesce to ~990,000 years ago, while the separation time between D and non-D is estimated at ~1,100,000 years ago. An evolutionary advantage of D is possible but controversial.[14]

The distribution of the D allele, high outside Africa but low in sub-Saharan Africa (29%), has been suggested to indicate involvement of an archaic Eurasian population, and current estimates of the divergence time between modern humans and Neanderthals based on mitochondrial DNA are in favor of the Neanderthal lineage as the most likely archaic Homo population from which introgression into the modern human gene pool took place.[15][16] However, according to Svante Pääbo, ancient DNA from Croatian Neanderthal fossils found at Vindija shows that they carried the non-D allele of microcephalin, and there is no evidence for admixture or introgression.[17][18] However a study published in May 2010 found that a Neanderthal individual from Mezzena Rockshelter (Monti Lessini, Italy), possessed the ancestral version of D, rather than the derived version which is common among Eurasian populations. The study did not rule out interbreeding between Neanderthals and modern humans, but indicates that the particular DNA sample provides no support to the theory that Neanderthals contributed the derived allele of D to modern humans.[19]

Based on a 2001 study of the gene that results in red-headedness,[20] some commentators speculated that Neanderthals had red hair and that some red-headed and freckled humans today share some heritage with Neanderthals.[21][22] A 2007 study analysing Neanderthal DNA found that some Neanderthals were red-haired, but the mutation to the MC1R gene which caused red hair in Neanderthals is not found in modern humans.[23]

There is evidence that some immune related genes are of Neanderthal origin. HLA-C*0702 is common in modern Europeans and Asians but rarely[24] seen in Africans, but is found in Neanderthals. It is thought that this immune gene may have been picked up by humans after leaving Africa to help deal with European diseases that the Neanderthals had evolved defenses for.[25]

The most vocal proponent of the hybridization hypothesis on anatomical grounds has been Erik Trinkaus of Washington University.[26] Trinkaus claims various fossils as hybrid individuals, including the "child of Lagar Velho", a skeleton found at Lagar Velho in Portugal dated to about 24,000 years ago.[27] In a 2006 publication co-authored by Trinkaus, the fossils found in 1952 in the cave of Pestera Muierii, Romania, are likewise claimed as hybrids. [28]

In his work Neanderthal, Paul Jordan points out that without some interbreeding, certain features on some "modern" skulls of Eastern European Cro-Magnon heritage are hard to explain.[29] In another study, researchers have recently found in Peştera Muierilor, Romania, remains of European humans from 30 thousand years ago who possessed mostly diagnostic "modern" anatomical features, but also had distinct Neanderthal features not present in ancestral modern humans in Africa, including a large bulge at the back of the skull, a more prominent projection around the elbow joint, and a narrow socket at the shoulder joint. Analysis of one skeleton's shoulder showed that these humans, like Neanderthal, did not have the full capability for throwing spears.[30]

The paleontological analysis of modern-human emergence in Europe has been shifting from considerations of the Neanderthals to assessments of the biology and chronology of the earliest modern humans in western Eurasia. This focus, involving morphologically modern humans before 28,000 years ago, shows accumulating evidence that they present a variable mosaic of derived modern human, archaic human, and Neanderthal features.[28][31][32] Studies of fossils from the upper levels of the Sima de las Palomas, Murcia, Spain, dated to 40,000 years ago, establish the late persistence of Neanderthals in Iberia. This reinforces the conclusion that the Neanderthals were not merely swept away by advancing modern humans. In addition, the Palomas Neanderthals variably exhibit a series of modern-human features rare or absent in earlier Neanderthals. Either they were evolving on their own towards the modern-human pattern, or more likely, they had contact with early modern humans around the Pyrenees. If the latter is the case, it implies that the persistence of the Middle Paleolithic in Iberia was a matter of choice, and not cultural retardation.[33]

Modern-human findings in Abrigo do Lagar Velho, Portugal, of 24,500 years ago, allegedly featuring Neanderthal admixtures, have been published.[34] However the interpretation of the Portuguese specimen is disputed.[35]

Tests comparing the Denisova hominingenome with those of six modern humans whose genome has been sequenced, a ǃKung from South Africa, a Nigerian, a French person, a Papua New Guinean, a Bougainville Islander and a Han Chinese showed that between 4% and 6% of the genome of Melanesians (represented by the Papua New Guinean and Bougainville Islander) derives from a Denisovan population, possibly introduced during the early migration of the ancestors of Melanesians into Southeast Asia. This history of interaction suggests that Denisovans once ranged widely over eastern Asia.[3]

Melanesians thus emerge as the most "archaic"-admixed population, having Denisovan/Neandertal-related admixture of ~8%.

Analysis of DNA data indicates that contemporary Sub-Saharan African populations contain a small percentage of genetic material from a now extinct archaic population (similar to the non-African admixture with Neanderthal and Denisova). The admixture occurred approximately 35,000 years ago with a archaic population that diverged from the ancestors of modern humans approximately 700,000 years ago. [36]